Endocrine Abstracts

Background: Carbohydrate loading is used to manage the neurovisceral attacks of the acute porphyrias. This presents difficulty when treating those with altered glucose homeostasis.

Case history: A 17-year-old female presented with 5 days of abdominal pain and vomiting, her third acute presentation in eight months; the first with a seizure and second with bilateral lower limb weakness. All attendances were preceded by reduced oral intake, strenuous physical exercise and surrounded her menses. She had antibody-negative diabetes diagnosed aged 14 with an Hba1c 73mmol/mol (20-41) and Hb 66g/l (120-150) at the time. C-peptide 2592 pmol/l (370-1470), MODY screen negative. There was a family history of type 2 diabetes. Aged 17, her BMI was 17.54kg/m2. She had acanthosis nigricans and hypercholesterolemia (total cholesterol 7.3mmol/l (0-5). She had stopped insulin and was normoglycaemic (Hba1c 35mmol/mol, haemoglobin 112g/l). Abdominal pain improved three days following cessation of menses and hyperglycaemia associated with improved oral intake necessitated restarting insulin. Sustained improvements in symptoms and biochemistry were seen. Urine porphobilinogen 28.5µmol/mmol (<1.5) confirmed an attack of acute porphyria.

Discussion: The acute porphyrias manifests as neurovisceral crises due to provoked build-up of neurotoxic heme precursors. Reduction in carbohydrate intake is a well-known trigger. Small observational studies report a high incidence of abnormal glucose homeostasis in those with acute porphyrias, with levels of insulin resistance positively associated with reduced disease activity. Molecular studies have shown that glucose and insulin downregulate heme synthesis synergistically, and a small clinical study reports clinical improvement with concomitant insulin and carbohydrate administration during an acute attack. Though the mechanism is not fully elucidated, hyperinsulinemia seems positively associated with clinical and biochemical disease activity. Therefore, insulin therapy alongside a carbohydrate rich diet may be a therapeutic option to support disease quiescence in those with acute porphyrias and altered glucose homeostasis without aggravating glycaemic control.